UW Neurological Surgery Recent PubMed Publications

IMPACT OF RETINAL ISCHEMIA ON FUNCTIONAL AND ANATOMICAL OUTCOMES AFTER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY IN PATIENTS WITH RETINAL VEIN OCCLUSION.

Retina. 2019 May 30;:

Authors: Khayat M, Wright DM, Yeong J, Xu D, Donley C, Lakshmipathy GR, Low MK, White N, Williams M, Lois N

Abstract
PURPOSE: To compare the impact of the classification of retinal vein occlusion (RVO) into ischemic or nonischemic forms on outcomes after anti-vascular endothelial growth factor therapy.
METHODS: Retrospective review of consecutive patients with RVO evaluated at the Belfast Health and Social Care Trust between July 1, 2014, and December 31, 2015. Outcomes, including gain of ≥10 and ≥15 letters at 12 months, mean change in best-corrected visual acuity from baseline to 12 months, resolution of macular edema at 12 months, and development of neovascular complications and epiretinal membrane after anti-vascular endothelial growth factor therapy, were compared between ischemic and nonischemic eyes using regression models.
RESULTS: One hundred and seventeen eyes (115 patients), 58 with central RVO and 59 with branch RVO, were included. A greater proportion of eyes with ischemic branch RVO gained ≥10 and ≥15 letters at 12 months than those with nonischemic branch RVO (P = 0.005 and P = 0.016, respectively). No statistically significant differences in visual outcomes were observed between ischemic and nonischemic central RVO. Retinal vein occlusion classification was not associated with anatomical outcomes after treatment.
CONCLUSION: Findings support the use of anti-vascular endothelial growth factors in ischemic and nonischemic forms of RVO.

PMID: 31157714 [PubMed - as supplied by publisher]

Recovery After Mild Traumatic Brain Injury in Patients Presenting to US Level I Trauma Centers: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Study.

JAMA Neurol. 2019 Jun 03;:

Authors: Nelson LD, Temkin NR, Dikmen S, Barber J, Giacino JT, Yuh E, Levin HS, McCrea MA, Stein MB, Mukherjee P, Okonkwo DO, Diaz-Arrastia R, Manley GT, and the TRACK-TBI Investigators, Adeoye O, Badjatia N, Boase K, Bodien Y, Bullock MR, Chesnut R, Corrigan JD, Crawford K, MIS, Duhaime AC, Ellenbogen R, Feeser VR, Ferguson A, Foreman B, Gardner R, Gaudette E, Gonzalez L, Gopinath S, Gullapalli R, Hemphill JC, Hotz G, Jain S, Korley F, Kramer J, Kreitzer N, Lindsell C, Machamer J, Madden C, Martin A, McAllister T, Merchant R, Noel F, Palacios E, Perl D, Puccio A, Rabinowitz M, Robertson CS, Rosand J, Sander A, Satris G, Schnyer D, Seabury S, Sherer M, Taylor S, Toga A, Valadka A, Vassar MJ, Vespa P, Wang K, Yue JK, Zafonte R

Abstract
Importance: Most traumatic brain injuries (TBIs) are classified as mild (mTBI) based on admission Glasgow Coma Scale (GCS) scores of 13 to 15. The prevalence of persistent functional limitations for these patients is unclear.
Objectives: To characterize the natural history of recovery of daily function following mTBI vs peripheral orthopedic traumatic injury in the first 12 months postinjury using data from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, and, using clinical computed tomographic (CT) scans, examine whether the presence (CT+) or absence (CT-) of acute intracranial findings in the mTBI group was associated with outcomes.
Design, Setting, and Participants: TRACK-TBI, a cohort study of patients with mTBI presenting to US level I trauma centers, enrolled patients from February 26, 2014, to August 8, 2018, and followed up for 12 months. A total of 1453 patients at 11 level I trauma center emergency departments or inpatient units met inclusion criteria (ie, mTBI [n = 1154] or peripheral orthopedic traumatic injury [n = 299]) and were enrolled within 24 hours of injury; mTBI participants had admission GCS scores of 13 to 15 and clinical head CT scans. Patients with peripheral orthopedic trauma injury served as the control (OTC) group.
Exposures: Participants with mTBI or OTC.
Main Outcomes and Measures: The Glasgow Outcome Scale Extended (GOSE) scale score, reflecting injury-related functional limitations across broad life domains at 2 weeks and 3, 6, and 12 months postinjury was the primary outcome. The possible score range of the GOSE score is 1 (dead) to 8 (upper good recovery), with a score less than 8 indicating some degree of functional impairment.
Results: Of the 1453 participants, 953 (65.6%) were men; mean (SD) age was 40.9 (17.1) years in the mTBI group and 40.9 (15.4) years in the OTC group. Most participants (mTBI, 87%; OTC, 93%) reported functional limitations (GOSE <8) at 2 weeks postinjury. At 12 months, the percentage of mTBI participants reporting functional limitations was 53% (95% CI, 49%-56%) vs 38% (95% CI, 30%-45%) for OTCs. A higher percentage of CT+ patients reported impairment (61%) compared with the mTBI CT- group (49%; relative risk [RR], 1.24; 95% CI, 1.08-1.43) and a higher percentage in the mTBI CT-group compared with the OTC group (RR, 1.28; 95% CI, 1.02-1.60).
Conclusions and Relevance: Most patients with mTBI presenting to US level I trauma centers report persistent, injury-related life difficulties at 1 year postinjury, suggesting the need for more systematic follow-up of patients with mTBI to provide treatments and reduce the risk of chronic problems after mTBI.

PMID: 31157856 [PubMed - as supplied by publisher]

The Impact of Cage Dimensions, Positioning, and Side of Approach in Extreme Lateral Interbody Fusion.

Clin Spine Surg. 2018 02;31(1):E42-E49

Authors: Alimi M, Lang G, Navarro-Ramirez R, Perrech M, Berlin C, Hofstetter CP, Moriguchi Y, Elowitz E, Härtl R

Abstract
STUDY DESIGN: This is a retrospective single-center study.
OBJECTIVE: The aim of the study was to evaluate the impact of cage characteristics and position toward clinical and radiographic outcome measures in patients undergoing extreme lateral interbody fusion (ELIF).
SUMMARY OF BACKGROUND DATA: ELIF is utilized for indirect decompression and minimally invasive surgical treatment for various degenerative spinal disorders. However, evidence regarding the influence of cage characteristics in patient outcome is minimal.
MATERIALS AND METHODS: Patients undergoing ELIF between 2007 and 2011 were included in a retrospective study. Demographic and perioperative data, as well as cage characteristics and side of approach were extracted. Radiographic parameters including lumbar lordosis, foraminal height, and disc height as well as clinical outcome parameters (Oswestry Disability Index and Visual Analog Scale) were measured preoperatively, postoperatively, and at the latest follow-up examination. Cage dimensions, in situ position, and type were correlated with radiographic and clinical outcome parameters.
RESULTS: In total, 84 patients with a total of 145 functional spinal units were analyzed. At the last follow-up of 17.7 months, radiographic and clinical outcome measures revealed significant improvement compared with before surgery with both, 18 and 22 mm cage anterior-posterior diameter subgroups (P≤0.05). Among cage characteristics, 22 mm cages presented superior restoration of foraminal and disc heights compared with 18 mm cages (P≤0.05). Neither position of the cage (anterior vs. posterior), nor the type (parallel vs. lordotic) had a significant impact on restoration of foraminal height and lumbar lordosis. Moreover, the side of surgical approach did not influence the amount of foraminal height increase.
CONCLUSIONS: Cage anterior-posterior diameter is the determining factor in restoration of foraminal height in ELIF. Cage height, type, positioning, and side of approach do not have a determining role in radiographic outcome in the present study. Sustainable foraminal height restoration is achieved by implantation of wider cages.
LEVEL OF EVIDENCE: Level 3.

PMID: 28319468 [PubMed - indexed for MEDLINE]

Reply to 'Assembling the brain trust: the multidisciplinary imperative in neuro-oncology'.

Nat Rev Clin Oncol. 2019 08;16(8):522-523

Authors: Aldape K, Brindle KM, Chesler L, Chopra R, Gajjar A, Gilbert MR, Gottardo N, Gutmann DH, Hargrave D, Holland EC, Jones DTW, Joyce JA, Kearns P, Kieran MW, Mellinghoff IK, Merchant M, Pfister SM, Pollard SM, Ramaswamy V, Rich JN, Robinson GW, Rowitch DH, Sampson JH, Taylor MD, Workman P, Gilbertson RJ

PMID: 31150022 [PubMed - indexed for MEDLINE]

Complex models of white and gray matter integration following training.

Cogn Neurosci. 2017 04;8(2):129-130

Authors: Williams JM

Abstract
For many tasks, an increase in competence is associated with faster response time. Voelker et al (this issue) explore the possible role of white matter reorganization as a mechanism underlying this relationship. With such a strong focus on this possible interpretation and the limits of current neuroimaging methods, the authors constrained their options to the point of only considering simplified models of how training might result in faster responses.

PMID: 27461454 [PubMed - indexed for MEDLINE]

Microsurgical and Endoscope Assisted Resection of a Right Intracanalicular Vestibular Schwannoma Two-Dimensional Operative Video.

J Neurol Surg B Skull Base. 2019 Jun;80(Suppl 3):S288-S289

Authors: Cheng CY, Qazi Z, Sekhar LN

Abstract
A 36-year-old lady presented with tinnitus and hearing loss for 1 year which was progressively worsening. A hearing test revealed pure tone average (PTA) between 48 to 65 dB and speech discrimination of 56% at 95 dB. Brain magnetic resonance imaging (MRI) showed a right vestibular schwannoma 5 × 8 mm ( Fig. 1 ) which extended far laterally to the fundus of internal auditory canal (IAC). A translabyrinthine approach was suggested by another neurosurgeon/neurotologist team, but the patient decided to undergo operation by retrosigmoid approach with attempted hearing preservation. She underwent a right retrosigmoid craniotomy, craniectomy, and mastoidectomy with far lateral approach. We performed petrous transcanalicular microsurgical approach with the assistance of neuroendoscope. Intraoperatively, the internal auditory artery was looping into the IAC between cranial nerves VII and VIII, and coming out inferiorly. The IAC was opened by the diamond drill, ultrasonic bone curette, and fine rongeurs. The tumor was grayish in color with filling the lateral aspect of the IAC. After circumferential dissection of the tumor capsule, the tumor was removed completely. It was arising from the inferior vestibular nerve which was stretched. The patient had vertigo and nausea postoperatively but it is steadily improving. Her hearing test has improved to a PTA of 22 dB and speech discrimination of 100% at 70 dB at 6 weeks. The postoperative MRI showed total resection. This two-dimensional video shows the technical nuances of microsurgical retrosigmoid approach and endoscopic assisted resection of an intracanalicular vestibular schwannoma and the value of attempting hearing preservation in all vestibular schwannomas ( Fig. 2 ). The link to the video can be found at: https://youtu.be/KHrO_iDI2tw .

PMID: 31143595 [PubMed]

Retrosigmoid Craniotomy for the Removal of Left Sided Tentorial and Posterior Fossa Meningioma Combined with Microvascular Decompression for Hemifacial Spasm.

J Neurol Surg B Skull Base. 2019 Jun;80(Suppl 3):S294-S295

Authors: Cheng YW, Cheng CY, Qazi Z, Sekhar LN

Abstract
This 68-year-old woman presented with repeated episodes of bilateral hemifacial spasm with headache for 5 years and with recent progression of left sided symptoms. Preoperative imaging showed a left sided tentorial meningioma with brain stem and cerebellar compression. Left facial nerve was compressed by the vertebral artery (VA) and the right facial nerve by the anterior inferior cerebellar artery (AICA). This patient underwent left side retrosigmoid craniotomy and mastoidectomy. The cisterna magna was drained to relax the brain. The tumor was very firm, attached to the tentorium and had medial and lateral lobules. The superior cerebellar artery was adherent to the lateral lobule of the tumor and dissected away. The tumor was detached from its tentorial base; we first removed the lateral lobule. Following this, the medial lobule was also completely dissected and removed. The root exit zone of cranial nerve (CN) VII was dissected and exposed. The compression was caused both by a prominent VA and AICA. Initially, the several pieces of Teflon felt were placed for the decompression. Then vertebropexy was performed by using 8-0 nylon suture placed through the VA media to the clival dura. A further piece of Teflon felt was placed between cerebellopontine angle region and AICA. Her hemifacial spasm resolved postoperatively, and she discharged home 1 week later. Postoperative imaging showed complete tumor removal and decompression of left CN VII. This video shows the complex surgery of microsurgical resection of a large tentorial meningioma and microvascular decompression with a vertebropexy procedure. The link to the video can be found at: https://youtu.be/N5aHN9CRJeM .

PMID: 31143598 [PubMed]

Decreases in smoking during treatment for methamphetamine-use disorders: preliminary evidence.

Behav Pharmacol. 2018 06;29(4):370-374

Authors: McPherson S, Orr M, Lederhos C, McDonell M, Leickly E, Hirchak K, Oluwoye OA, Murphy SM, Layton M, Roll JM

Abstract
Despite high rates of smoking (70-90%) and the severely negative impact of smoking on physical and mental health, only 12% of individuals receiving stimulant-use disorder treatment also receive smoking-cessation treatment. The aim of this investigation was to examine the effect of a contingency management (CM) intervention targeting methamphetamine (MA) use on cigarette smoking. Sixty-one adults with MA-use disorders who were smokers were assigned to CM or standard psychosocial treatment. Rates of smoking-negative breath samples (carbon monoxide <3 ppm) were compared between the two groups while controlling for baseline carbon monoxide level, marijuana use, MA use, and time. This subgroup of mostly male (59%) participants included 44 participants in the CM group and 17 participants in the standard psychosocial treatment. Tobacco smoking participants who received CM targeting MA use were 140% (odds ratio: 2.395; 95% confidence interval: 1.073-5.346) more likely to submit a smoking-negative breath sample relative to standard psychosocial treatment during the treatment period, holding constant several other prespecified covariates. This study provides evidence that a behavioral treatment for MA use results in reductions in cigarette smoking in adults with MA-use disorder.

PMID: 29035917 [PubMed - indexed for MEDLINE]

Loss of Intercalated Cells (ITCs) in the Mouse Amygdala of Tshz1 Mutants Correlates with Fear, Depression, and Social Interaction Phenotypes.

J Neurosci. 2018 01 31;38(5):1160-1177

Authors: Kuerbitz J, Arnett M, Ehrman S, Williams MT, Vorhees CV, Fisher SE, Garratt AN, Muglia LJ, Waclaw RR, Campbell K

Abstract
The intercalated cells (ITCs) of the amygdala have been shown to be critical regulatory components of amygdalar circuits, which control appropriate fear responses. Despite this, the molecular processes guiding ITC development remain poorly understood. Here we establish the zinc finger transcription factor Tshz1 as a marker of ITCs during their migration from the dorsal lateral ganglionic eminence through maturity. Using germline and conditional knock-out (cKO) mouse models, we show that Tshz1 is required for the proper migration and differentiation of ITCs. In the absence of Tshz1, migrating ITC precursors fail to settle in their stereotypical locations encapsulating the lateral amygdala and BLA. Furthermore, they display reductions in the ITC marker Foxp2 and ectopic persistence of the dorsal lateral ganglionic eminence marker Sp8. Tshz1 mutant ITCs show increased cell death at postnatal time points, leading to a dramatic reduction by 3 weeks of age. In line with this, Foxp2-null mutants also show a loss of ITCs at postnatal time points, suggesting that Foxp2 may function downstream of Tshz1 in the maintenance of ITCs. Behavioral analysis of male Tshz1 cKOs revealed defects in fear extinction as well as an increase in floating during the forced swim test, indicative of a depression-like phenotype. Moreover, Tshz1 cKOs display significantly impaired social interaction (i.e., increased passivity) regardless of partner genetics. Together, these results suggest that Tshz1 plays a critical role in the development of ITCs and that fear, depression-like and social behavioral deficits arise in their absence.SIGNIFICANCE STATEMENT We show here that the zinc finger transcription factor Tshz1 is expressed during development of the intercalated cells (ITCs) within the mouse amygdala. These neurons have previously been shown to play a crucial role in fear extinction. Tshz1 mouse mutants exhibit severely reduced numbers of ITCs as a result of abnormal migration, differentiation, and survival of these neurons. Furthermore, the loss of ITCs in mouse Tshz1 mutants correlates well with defects in fear extinction as well as the appearance of depression-like and abnormal social interaction behaviors reminiscent of depressive disorders observed in human patients with distal 18q deletions, including the Tshz1 locus.

PMID: 29255003 [PubMed - indexed for MEDLINE]

Adjuvant Therapy for Ampullary Cancer.

JAMA Surg. 2019 08 01;154(8):715

Authors: Ko AH, Nakakura EK

PMID: 31141140 [PubMed - indexed for MEDLINE]

Impairment of cognitive flexibility in type 2 diabetic db/db mice.

Behav Brain Res. 2019 10 03;371:111978

Authors: Yermakov LM, Griggs RB, Drouet DE, Sugimoto C, Williams MT, Vorhees CV, Susuki K

Abstract
Impaired executive function is a major peril for patients with type 2 diabetes, reducing quality of life and ability for diabetes management. Despite the significance of this impairment, few animal models of type 2 diabetes examine domains of executive function such as cognitive flexibility or working memory. Here, we evaluated these executive function domains in db/db mice, an established model of type 2 diabetes, at 10 and 24 weeks of age. The db/db mice showed impaired cognitive flexibility in the Morris water maze reversal phase. However, the db/db mice did not show apparent working memory disturbance in the spatial working memory version of the Morris water maze or in the radial water maze. We also examined axon initial segments (AIS) and nodes of Ranvier, key axonal domains for action potential initiation and propagation. AIS were significantly shortened in medial prefrontal cortex and hippocampus of 26-week-old db/db mice compared with controls, similar to our previous findings in 10-week-old mice. Nodes of Ranvier in corpus callosum, previously shown to be unchanged at 10 weeks, were elongated at 26 weeks, suggesting an important role for this domain in disease progression. Together, the findings help establish db/db mice as a model of impaired cognitive flexibility in type 2 diabetes and advance our understanding of its pathophysiology.

PMID: 31141724 [PubMed - indexed for MEDLINE]

Evolution of Bandeau Shape, Orbital Morphology, and Craniofacial Twist after Fronto-Orbital Advancement for Isolated Unilateral Coronal Synostosis: A Case-Control Study of 2-Year Outcomes.

Plast Reconstr Surg. 2019 06;143(6):1703-1711

Authors: Liu MT, Khechoyan DY, Susarla SM, Skladman R, Birgfeld CB, Gruss JS, Lee A, Ellenbogen RG, Pet MA, Hopper RA

Abstract
BACKGROUND: The authors' purpose was to quantify the change in unicoronal synostosis symmetry between presentation (time 0), after fronto-orbital advancement (time 1), and 2 years later (time 2).
METHODS: Bandeau/orbital symmetry ratios and skull base/midface twists were measured on computed tomographic scans of consecutive isolated unicoronal synostosis patients. Comparisons were made across three time points and against normal controls.
RESULTS: Forty-three unicoronal synostosis patients and 36 controls were included. The mean bandeau ratio (symmetry = 1) changed from 0.76 (time 0), to 1.13 (time 1), and then to 1.01 (time 2). The median bandeau ratio change from time 1 to time 2 was -9.1 percent and was impacted by the degree of time 1 asymmetry. The odds of a desired symmetric or overcorrected result (bandeau ratio > 1.0) at time 2 were increased in patients with less severe preoperative asymmetry (OR, 4.2; p = 0.04) and in those who obtained symmetry or overcorrection at surgery (OR, 4.9; p = 0.02). Craniofacial twist did not significantly change after surgery but decreased at time 2. Orbital height ratios were 1.08, 1.00, and then 1.02 at time 2, respectively. The orbital width ratio was not significantly impacted by surgery, remaining at 0.89 at time 2.
CONCLUSIONS: Overcorrection of the unicoronal synostosis bandeau resulted in these patients being five times more likely to have a desired result at time 2. Patients with a more severe brow presentation were four times more likely to be asymmetric at time 2. Orbital height was improved, but attention should be directed at addressing orbital width.
CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

PMID: 31136486 [PubMed - indexed for MEDLINE]

The clinical spectrum of hydrocephalus in adults: report of the first 517 patients of the Adult Hydrocephalus Clinical Research Network registry.

J Neurosurg. 2019 May 24;:1-12

Authors: Williams MA, Nagel SJ, Luciano MG, Relkin N, Zwimpfer TJ, Katzen H, Holubkov R, Moghekar A, Wisoff JH, McKhann GM, Golomb J, Edwards RJ, Hamilton MG

Abstract
OBJECTIVEThe authors describe the demographics and clinical characteristics of the first 517 patients enrolled in the Adult Hydrocephalus Clinical Research Network (AHCRN) during its first 2 years.METHODSAdults ≥ 18 years were nonconsecutively enrolled in a registry at 6 centers. Four categories of adult hydrocephalus were defined: transition (treated before age 18 years), unrecognized congenital (congenital pattern, not treated before age 18 years), acquired (secondary to known risk factors, treated or untreated), and suspected idiopathic normal pressure hydrocephalus (iNPH) (≥ age 65 years, not previously treated). Data include etiology, symptoms, examination findings, neuropsychology screening, comorbidities, treatment, complications, and outcomes. Standard evaluations were administered to all patients by trained examiners, including the Montreal Cognitive Assessment, the Symbol Digit Modalities Test, the Beck Depression Inventory-II, the Overactive Bladder Questionnaire Short Form symptom bother, the 10-Meter Walk Test, the Boon iNPH gait scale, the Lawton Activities of Daily Living/Instrumental Activities of Daily Living (ADL/IADL) questionnaire, the iNPH grading scale, and the modified Rankin Scale.RESULTSOverall, 517 individuals were enrolled. Age ranged from 18.1 to 90.7 years, with patients in the transition group (32.7 ± 10.0 years) being the youngest and those in the suspected iNPH group (76.5 ± 5.2 years) being the oldest. The proportion of patients in each group was as follows: 16.6% transition, 26.5% unrecognized congenital, 18.2% acquired, and 38.7% suspected iNPH. Excluding the 86 patients in the transition group, who all had received treatment, 79.4% of adults in the remaining 3 groups had not been treated at the time of enrollment. Patients in the suspected iNPH group had the poorest performance in cognitive evaluations, and those in the unrecognized congenital group had the best performance. The same pattern was seen in the Lawton ADL/IADL scores. Gait velocity was lowest in patients in the suspected iNPH group. Categories that had the most comorbidities (suspected iNPH) or etiologies of hydrocephalus that directly cause neurological injury (transition, acquired) had greater degrees of impairment compared to unrecognized congenital, which had the fewest comorbidities or etiologies associated with neurological injury.CONCLUSIONSThe clinical spectrum of hydrocephalus in adults comprises more than iNPH or acquired hydrocephalus. Only 39% of patients had suspected iNPH, whereas 43% had childhood onset (i.e., those in the transition and unrecognized congenital groups). The severity of symptoms and impairment was worsened when the etiology of the hydrocephalus or complications of treatment caused additional neurological injury or when multiple comorbidities were present. However, more than half of patients in the transition, unrecognized congenital, and acquired hydrocephalus groups had minimal or no impairment. Excluding the transition group, nearly 80% of patients in the AHCRN registry were untreated at the time of enrollment. A future goal for the AHCRN is to determine whether patients with unrecognized congenital and acquired hydrocephalus need treatment and which patients in the suspected iNPH cohort actually have possible hydrocephalus and should undergo further diagnostic testing. Future prospective research is needed in the diagnosis, treatment, outcomes, quality of life, and macroeconomics of all categories of adult hydrocephalus.

PMID: 31125971 [PubMed - as supplied by publisher]

Results from a Phase IIb, Randomized, Multicenter Study of GVAX Pancreas and CRS-207 Compared with Chemotherapy in Adults with Previously Treated Metastatic Pancreatic Adenocarcinoma (ECLIPSE Study).

Clin Cancer Res. 2019 Sep 15;25(18):5493-5502

Authors: Le DT, Picozzi VJ, Ko AH, Wainberg ZA, Kindler H, Wang-Gillam A, Oberstein P, Morse MA, Zeh HJ, Weekes C, Reid T, Borazanci E, Crocenzi T, LoConte NK, Musher B, Laheru D, Murphy A, Whiting C, Nair N, Enstrom A, Ferber S, Brockstedt DG, Jaffee EM

Abstract
PURPOSE: Limited options exist for patients with advanced pancreatic cancer progressing after 1 or more lines of therapy. A phase II study in patients with previously treated metastatic pancreatic cancer showed that combining GVAX pancreas (granulocyte-macrophage colony-stimulating factor-secreting allogeneic pancreatic tumor cells) with cyclophosphamide (Cy) and CRS-207 (live, attenuated Listeria monocytogenes expressing mesothelin) resulted in median overall survival (OS) of 6.1 months, which compares favorably with historical OS achieved with chemotherapy. In the current study, we compared Cy/GVAX + CRS-207, CRS-207 alone, and standard chemotherapy in a three-arm, randomized, controlled phase IIb trial.
PATIENTS AND METHODS: Patients with previously treated metastatic pancreatic adenocarcinoma were randomized 1:1:1 to receive Cy/GVAX + CRS-207 (arm A), CRS-207 (arm B), or physician's choice of single-agent chemotherapy (arm C). The primary cohort included patients who had failed ≥2 prior lines of therapy, including gemcitabine. The primary objective compared OS between arms A and C in the primary cohort. The second-line cohort included patients who had received 1 prior line of therapy. Additional objectives included OS between all treatment arms, safety, and tumor responses.
RESULTS: The study did not meet its primary efficacy endpoint. At the final study analysis, median OS [95% confidence interval (CI)] in the primary cohort (N = 213) was 3.7 (2.9-5.3), 5.4 (4.2-6.4), and 4.6 (4.2-5.7) months in arms A, B, and C, respectively, showing no significant difference between arm A and arm C [P = not significant (NS), HR = 1.17; 95% CI, 0.84-1.64]. The most frequently reported adverse events in all treatment groups were chills, pyrexia, fatigue, and nausea. No treatment-related deaths occurred.
CONCLUSIONS: The combination of Cy/GVAX + CRS-207 did not improve survival over chemotherapy. (ClinicalTrials.gov ID: NCT02004262)See related commentary by Salas-Benito et al., p. 5435.

PMID: 31126960 [PubMed - indexed for MEDLINE]

Neurophysiological evidence for early modulation of amygdala activity by emotional reappraisal.

Biol Psychol. 2019 07;145:211-223

Authors: Guex R, Hofstetter C, Domínguez-Borràs J, Méndez-Bértolo C, Sterpenich V, Spinelli L, Seeck M, Vuilleumier P

Abstract
How emotions unfold through time in the brain, and how fast they can be regulated by voluntary control, remain unresolved. Psychological accounts of emotion regulation posit cognitive reappraisal mechanisms may alter early emotion generative processes directly, whereas suppression impacts only later processing stages, after emotion has arisen. However, to date, there is no neurophysiological data concerning the precise latency of emotion regulation effects on the amygdala, a major emotion processing relay in the brain. Here we record amygdala activity from six patients undergoing surgery for pharmaco-resistant epilepsy during both reappraisal and suppression. We find that emotion reappraisal strategy, but not suppression, modulates early neural responses to emotional scenes during an extended period of time, starting 130 ms post-stimulus onset. Further, reappraisal produced earlier impact on amygdala responses to positive compared to negative scenes. Our results provide the first neurophysiological support for theoretical accounts of emotion regulation that postulate an early modulation of emotion generative processes by reappraisal.

PMID: 31129312 [PubMed - indexed for MEDLINE]

Promoting physical activity in regional and remote cancer survivors (PPARCS) using wearables and health coaching: randomised controlled trial protocol.

BMJ Open. 2019 05 24;9(5):e028369

Authors: Hardcastle SJ, Hince D, Jiménez-Castuera R, Boyle T, Cavalheri V, Makin G, Tan P, Salfinger S, Tan J, Mohan GR, Levitt M, Cohen PA, Saunders C, Platell C

Abstract
INTRODUCTION: Physically active cancer survivors have substantially less cancer recurrence and improved survival compared with those who are inactive. However, the majority of survivors (70%-90%) are not meeting the physical activity (PA) guidelines. There are also significant geographic inequalities in cancer survival with poorer survival rates for the third of Australians who live in non-metropolitan areas compared with those living in major cities. The primary objective of the trial is to increase moderate-to-vigorous PA (MVPA) among cancer survivors living in regional and remote Western Australia. Secondary objectives are to reduce sedentary behaviour and in conjunction with increased PA, improve quality of life (QoL) in non-metropolitan survivors. Tertiary objectives are to assess the effectiveness of the health action process approach (HAPA) model variables, on which the intervention is based, to predict change in MVPA.
METHODS AND ANALYSIS: Eighty-six cancer survivors will be randomised into either the intervention or control group. Intervention group participants will receive a Fitbit and up to six telephone health-coaching sessions. MVPA (using Actigraph), QoL and psychological variables (based on the HAPA model via questionnaire) will be assessed at baseline, 12 weeks (end of intervention) and 24 weeks (end of follow-up). A general linear mixed model will be used to assess the effectiveness of the intervention.
ETHICS AND DISSEMINATION: Ethics approval has been obtained from St John of God Hospital Subiaco (HREC/#1201). We plan to submit a manuscript of the results to a peer-reviewed journal. Results will be presented at conferences, community and consumer forums and hospital research conferences.
TRIAL REGISTRATION NUMBER: ACTRN12618001743257; pre-results, U1111-1222-5698.

PMID: 31129600 [PubMed - indexed for MEDLINE]

Consensus statement from the International Consensus Meeting on the Role of Decompressive Craniectomy in the Management of Traumatic Brain Injury : Consensus statement.

Acta Neurochir (Wien). 2019 07;161(7):1261-1274

Authors: Hutchinson PJ, Kolias AG, Tajsic T, Adeleye A, Aklilu AT, Apriawan T, Bajamal AH, Barthélemy EJ, Devi BI, Bhat D, Bulters D, Chesnut R, Citerio G, Cooper DJ, Czosnyka M, Edem I, El-Ghandour NMF, Figaji A, Fountas KN, Gallagher C, Hawryluk GWJ, Iaccarino C, Joseph M, Khan T, Laeke T, Levchenko O, Liu B, Liu W, Maas A, Manley GT, Manson P, Mazzeo AT, Menon DK, Michael DB, Muehlschlegel S, Okonkwo DO, Park KB, Rosenfeld JV, Rosseau G, Rubiano AM, Shabani HK, Stocchetti N, Timmons SD, Timofeev I, Uff C, Ullman JS, Valadka A, Waran V, Wells A, Wilson MH, Servadei F

Abstract
BACKGROUND: Two randomised trials assessing the effectiveness of decompressive craniectomy (DC) following traumatic brain injury (TBI) were published in recent years: DECRA in 2011 and RESCUEicp in 2016. As the results have generated debate amongst clinicians and researchers working in the field of TBI worldwide, it was felt necessary to provide general guidance on the use of DC following TBI and identify areas of ongoing uncertainty via a consensus-based approach.
METHODS: The International Consensus Meeting on the Role of Decompressive Craniectomy in the Management of Traumatic Brain Injury took place in Cambridge, UK, on the 28th and 29th September 2017. The meeting was jointly organised by the World Federation of Neurosurgical Societies (WFNS), AO/Global Neuro and the NIHR Global Health Research Group on Neurotrauma. Discussions and voting were organised around six pre-specified themes: (1) primary DC for mass lesions, (2) secondary DC for intracranial hypertension, (3) peri-operative care, (4) surgical technique, (5) cranial reconstruction and (6) DC in low- and middle-income countries.
RESULTS: The invited participants discussed existing published evidence and proposed consensus statements. Statements required an agreement threshold of more than 70% by blinded voting for approval.
CONCLUSIONS: In this manuscript, we present the final consensus-based recommendations. We have also identified areas of uncertainty, where further research is required, including the role of primary DC, the role of hinge craniotomy and the optimal timing and material for skull reconstruction.

PMID: 31134383 [PubMed - indexed for MEDLINE]

The Cost of Inflammatory Bowel Disease: An Initiative From the Crohn's & Colitis Foundation.

Inflamm Bowel Dis. 2020 01 01;26(1):1-10

Authors: Park KT, Ehrlich OG, Allen JI, Meadows P, Szigethy EM, Henrichsen K, Kim SC, Lawton RC, Murphy SM, Regueiro M, Rubin DT, Engel-Nitz NM, Heller CA

Abstract
BACKGROUND: The Crohn's & Colitis Foundation's Cost of Inflammatory Bowel Disease (IBD) Care Initiative seeks to quantify the wide-ranging health care costs affecting patients living with IBD. We aimed to (1) describe the annualized direct and indirect costs of care for patients with Crohn's disease (CD) or ulcerative colitis (UC), (2) determine the longitudinal drivers of these costs, and (3) characterize the cost of care for newly diagnosed patients.
METHODS: We analyzed the Optum Research Database from the years 2007 to 2016, representing commercially insured and Medicare Advantage-insured patients in the United States. Inclusion for the study was limited to those who had continuous enrollment with medical and pharmacy benefit coverage for at least 24 months (12 months before through 12 months after the index date of diagnosis). The value of patient time spent on health care was calculated as number of workplace hours lost due to health care encounters multiplied by the patients' estimated average wage derived from the Bureau of Labor Statistics. Comparisons between IBD patients and non-IBD patients were analyzed based on demographics, health plan type, and length of follow-up. We used generalized linear models to estimate the association between total annual costs and various patient variables.
RESULTS: There were 52,782 IBD patients (29,062 UC; 23,720 CD) included in the analysis (54.1% females). On a per-annual basis, patients with IBD incurred a greater than 3-fold higher direct cost of care compared with non-IBD controls ($22,987 vs $6956 per-member per-year paid claims) and more than twice the out-of-pocket costs ($2213 vs $979 per-year reported costs), with all-cause IBD costs rising after 2013. Patients with IBD also experienced significantly higher costs associated with time spent on health care as compared with controls. The burden of costs was most notable in the first year after initial IBD diagnosis (mean = $26,555). The study identified several key drivers of cost for IBD patients: treatment with specific therapeutics (biologics, opioids, or steroids); ED use; and health care services associated with relapsing disease, anemia, or mental health comorbidity.
CONCLUSION: The costs of care for IBD have increased in the last 5 years and are driven by specific therapeutics and disease features. In addition, compared with non-IBD controls, IBD patients are increasingly incurring higher costs associated with health care utilization, out-of-pocket expenditures, and workplace productivity losses. There is a pressing need for cost-effective strategies to address these burdens on patients and families affected by IBD.

PMID: 31112238 [PubMed - indexed for MEDLINE]

Effects of surgical targeting in laser interstitial thermal therapy for mesial temporal lobe epilepsy: A multicenter study of 234 patients.

Epilepsia. 2019 06;60(6):1171-1183

Authors: Wu C, Jermakowicz WJ, Chakravorti S, Cajigas I, Sharan AD, Jagid JR, Matias CM, Sperling MR, Buckley R, Ko A, Ojemann JG, Miller JW, Youngerman B, Sheth SA, McKhann GM, Laxton AW, Couture DE, Popli GS, Smith A, Mehta AD, Ho AL, Halpern CH, Englot DJ, Neimat JS, Konrad PE, Neal E, Vale FL, Holloway KL, Air EL, Schwalb J, Dawant BM, D'Haese PF

Abstract
OBJECTIVE: Laser interstitial thermal therapy (LITT) for mesial temporal lobe epilepsy (mTLE) has reported seizure freedom rates between 36% and 78% with at least 1 year of follow-up. Unfortunately, the lack of robust methods capable of incorporating the inherent variability of patient anatomy, the variability of the ablated volumes, and clinical outcomes have limited three-dimensional quantitative analysis of surgical targeting and its impact on seizure outcomes. We therefore aimed to leverage a novel image-based methodology for normalizing surgical therapies across a large multicenter cohort to quantify the effects of surgical targeting on seizure outcomes in LITT for mTLE.
METHODS: This multicenter, retrospective cohort study included 234 patients from 11 centers who underwent LITT for mTLE. To investigate therapy location, all ablation cavities were manually traced on postoperative magnetic resonance imaging (MRI), which were subsequently nonlinearly normalized to a common atlas space. The association of clinical variables and ablation location to seizure outcome was calculated using multivariate regression and Bayesian models, respectively.
RESULTS: Ablations including more anterior, medial, and inferior temporal lobe structures, which involved greater amygdalar volume, were more likely to be associated with Engel class I outcomes. At both 1 and 2 years after LITT, 58.0% achieved Engel I outcomes. A history of bilateral tonic-clonic seizures decreased chances of Engel I outcome. Radiographic hippocampal sclerosis was not associated with seizure outcome.
SIGNIFICANCE: LITT is a viable treatment for mTLE in patients who have been properly evaluated at a comprehensive epilepsy center. Consideration of surgical factors is imperative to the complete assessment of LITT. Based on our model, ablations must prioritize the amygdala and also include the hippocampal head, parahippocampal gyrus, and rhinal cortices to maximize chances of seizure freedom. Extending the ablation posteriorly has diminishing returns. Further work is necessary to refine this analysis and define the minimal zone of ablation necessary for seizure control.

PMID: 31112302 [PubMed - indexed for MEDLINE]

The authors reply.

Crit Care Med. 2017 11;45(11):e1194-e1195

Authors: Krishnamoorthy V, Rowhani-Rahbar A, Gibbons EF, Rivara FP, Temkin NR, Chaikittisilpa N, Luk K, Vavilala MS

PMID: 29028720 [PubMed - indexed for MEDLINE]